%0 Journal Article
%T Autophagy Mechanism, Regulation, Functions, and Disorders
%A Mallikarjun Badadani
%J ISRN Cell Biology
%D 2012
%R 10.5402/2012/927064
%X Autophagy is a self-digesting mechanism responsible for removal of damaged organelles, malformed proteins during biosynthesis, and nonfunctional long-lived proteins by lysosome. Autophagy has been divided into three general types depending on the mechanism by which intracellular materials are delivered into lysosome for degradation that is, microautophagy, chaperone-mediated autophagy (CMA), and macroautophagy. In microautophagy cytoplasm material is sequestered through direct invagination to the lysosomal membrane. Whereas in CMA proteins flagged with pentapeptide motif (KFERQ) were selectively degraded through direct translocation into lysosome. Macroautophagy involves the formation of subcellular double-membrane-bound structures called autophagosomes that contain degradable contents of cytoplasm materials and deliver them into lysosomes for breakdown by lysosomal enzymes. The molecular mechanism of autophagy involves several conserved Atg (autophagy-related) proteins. Systems produce modified complexes Atg8-PE and Atg5-Atg12-Atg16 as autophagy regulators. Autophagy is activated in response to diverse stress and physiological conditions. For example, food deprivation, hyperthermia, and hypoxia are mediated by factors like insulin/IGF-1, m-TOR signaling, FOXO transcription factors, and chaperones. The perturbance in autophagy may lead to several types of cancers, myopathies, and neuromuscular disorders. Several autophagy inducers and inhibitors like 3-methyladenine (3-MA), bafilomycin A1, LY294002 (LY), and Velcade have been used to treat disease is an intense field of study. 1. What Is Autophagy? Before delving into the aspects of autophagy, There ia a well-known answer to the question: What is an autophagy? In the current science, autophagy is a self-digesting mechanism responsible for removal of long-lived proteins, damaged organelles, and malformed proteins during biosynthesis by lysosome [1¨C3]. The evidence demonstrates that autophagic process is meant for regulating diverse cellular functions including growth, differentiation, response to nutrient deficit and oxidative stress, cell death, and macromolecule and organelle turnover. 2. Autophagy Mechanism Autophagy involves the formation of a double-membrane vesicle, which encapsulates cytoplasm, malformed proteins, long-lived proteins, and organelles and then fuses with lysosomes for degradation. The formation of the double-membrane vesicle is a complex process involving 16 autophagy-related proteins (Atg proteins). Apart from this, two ubiquitin-like conjugation systems are involved in autophagy.
%U http://www.hindawi.com/journals/isrn.cell.biology/2012/927064/